Not so fast: adaptive suppression of innate immunity

Abstract

The innate and adaptive immune systems act in concert to effectively combat infection while minimizing collater al damage caused by the host immune response. T cells of the adaptive immune system have now been shown to suppress overzealous early innate responses to infection that can lead to 'cytokine storm'–mediated death (pages 1248–1252).

Figure 1. Conventional T cells suppress overzealous early innate responses, thus preventing severe immunopathology.

In response to infection or to purified pathogen-associated molecular patterns, TLRs on macrophages and dendritic cells (DCs) of the innate immune system are activated, inducing the production of inflammatory cytokines, such as TNFα. (a) In wild-type mice, conventional T cells of the adaptive immune system suppress early inflammatory cytokine production by innate cells in a contact- and MHC class II–dependent manner; regulatory T cells can also suppress innate cytokine production similarly (not shown). The precise mechanism of suppression, however, is unclear. (b) Nude mice, which are deficient in T cells, or Rag-deficient mice, which lack all adaptive immunity, are unable to control the early innate response to infection or to pathogen-associated molecular patterns. In the absence of T-cell–mediated regulation of innate immunity, an overzealous early innate response characterized by the overproduction of TNFα can lead to severe immunopathology and death. Kim Caesar